Early-stage Lesions Research Articles

Clinical and pathological findings of chronic actinic dermatitis.

Chronic actinic dermatitis (CAD) is a recurrent photosensitive disease occurs predominantly in elderly men on sun-exposed areas, which seriously affect the patient's life quality. The etiology of CAD remains unknown. Sixty-six CAD patients, 66 atopic dermatitis (AD) patients, and 46 healthy people were enrolled into this study. Patient-level data were obtained from the electronic medical record and laboratory databases. We also obtained 29 tissue samples including 16 lichenoid lesions, 7 minimal erythematous dose (MED) analysis induced lesions, and 6 normal skin samples. Histopathologic and immunohistochemical analysis were performed. In the clinical characteristics, albumin was lower and uric acid was higher significantly in patients diagnosed as CAD. The infection rate of CAD patient after skin biopsy was considerably high (23.3%). The serum allergen test was prone to be negative in CAD patients. Lymphocytes were the dominate infiltrating cells in early and late CAD lesions, while more CD4+, CD8+, CD69+, and CD103+cells were found in the late lesions. There is no difference in CD4+/CD8+ratio and CD69+/CD103+ratio among groups. More mast cells were observed in the early-stage lesions, and more dendritic cell was observed in the late-stage lesions. CAD patients have certain oxidative stress and are prone to be infected after skin biopsy. Serum allergen detection is of little significance for CAD diagnosis. Mast cells may be involved in the early process of CAD, while dendritic cells and tissue-resident memory T cell (TRM) may be related to the chronic process of the disease.

Transanal endoscopic microsurgery: exploring its indications and novel applications. A narrative review.

Featuring some advantages of endoscopy and microsurgery, transanal endoscopic microsurgery (TEM) was first introduced in treating local early-stage rectal lesions in 1983. However, its applications to rectal surgery have remained virtually unchanged over the past 38 years. This review aims to describe some well-accepted indications for TEM and showcase other novel but successful applications. In this review, we conducted a thorough English literature review on the applications of transanal endoscopic microsurgery in the PubMed database. Published original articles, case reports, and letters from 1983 to 2020 were included. Retrieved articles were discussed and conclusions were made. The results showed that applications of TEM could be more flexible and extended, namely, TEM’s niche applications in advanced rectal cancer after neoadjuvant chemoradiotherapy, neuroendocrine tumor, gastrointestinal stromal tumor, fistula, solitary rectal ulcer syndrome, benign stricture, and transanal total mesorectal excision are promising, while prospective studies are needed.

English

BACKGROUND Most commonly occurring impacted teeth encountered in dental surgery are mandibular 3rd molars. Reasons of impactions may be due to evolution and modern dietary habits, lack of space, decreased skeletal growth, and disproportionate crown size. Impacted tooth may cause various complications, if left untreated distal caries is commonly seen in mandibular 2nd molars. The aim of the current study was to determine the prevalence of distal caries of mandibular 2nd molars due to impacted mandibular 3rd molars. Symptoms like distal caries of 2rd molars is one of the major factors affecting the oral health next to periodontal disease and periodontal abscess. METHODS The study included 103 patients, reported to the dental department of Tripura Medical College and BRAM &Teaching Hospital, Agartala. The study was done from July 2019 – December 2019, age ranged from 18 to 50 years. Panoramic radiographic examinations were carried out in each patient. Angulations of impaction and incidence of caries of the adjacent mandibular 2nd molars were recorded. All data were collected and analysed using percentage analysis. RESULTS 103 patients panoramic radiographs were studied, out of 103, 63 (61 %) were male, 40 (39 %) were female. 31 patients (30.1 %) out of 103 patients were found to have distal caries of mandibular 2nd molars adjacent to mandibular 3nd molars. 85 % of caries was associated with mesioangular impaction. CONCLUSIONS Careful monitoring to detect the caries lesions in early stage is necessary, as the distal caries on the mandibular 2nd molars was found to be high. Subsequently proper measures should be taken for restoration of mandibular 2nd molars and removal of impacted mandibular 3rd molars, if necessary. KEYWORDS Distal Surface Caries, Mandibular 2nd Molars, Impacted Mandibular 3rd Molars, Angulation

Men1 disruption in Nkx3.1-deficient mice results in ARlow/CD44+ microinvasive carcinoma development with the dysregulated AR pathway.

Dysregulated androgen receptor (AR) plays a crucial role in prostate cancer (PCa) development, though further factors involved in its regulation remain to be identified. Recently, paradoxical results were reported on the implication of the MEN1 gene in PCa. To dissect its role in prostate luminal cells, we generated a mouse model with inducible Men1 disruption in Nkx3.1-deficient mice in which mouse prostatic intraepithelial neoplasia (mPIN) occur. Prostate glands from mutant and control mice were analyzed pathologically and molecularly; cellular and molecular analyses were carried out in PCa cell lines after MEN1 knockdown (KD) by siRNA. Double-mutant mice developed accelerated mPIN and later displayed microinvasive adenocarcinoma. Markedly, early-stage lesions exhibited a decreased expression of AR and its target genes, accompanied by reduced CK18 and E-cadherin expression, suggesting a shift from a luminal to a dedifferentiated epithelial phenotype. Intriguingly, over 60% of menin-deficient cells expressed CD44 at a later stage. Furthermore, MEN1 KD led to the increase in CD44 expression in PC3 cells re-expressing AR. Menin bound to the proximal AR promoter and regulated AR transcription via the H3K4me3 histone mark. Interestingly, the cell proliferation of AR-dependent cells (LNCaP, 22Rv1, and VCaP), but not of AR-independent cells (DU145, PC3), responded strongly to MEN1 silencing. Finally, menin expression was found reduced in some human PCa. These findings highlight the regulation of the AR promoter by menin and the crosstalk between menin and the AR pathway. Our data could be useful for better understanding the increasingly reported AR-negative/NE-negative subtype of PCa and the mechanisms underlying its development.

Excitation-scanning hyperspectral video endoscopy: enhancing the light at the end of the tunnel.

Colorectal cancer is the 3rd leading cancer for incidence and mortality rates. Positive treatment outcomes have been associated with early detection; however, early stage lesions have limited contrast to surrounding mucosa. A potential technology to enhance early stagise detection is hyperspectral imaging (HSI). While HSI technologies have been previously utilized to detect colorectal cancer ex vivo or post-operation, they have been difficult to employ in real-time endoscopy scenarios. Here, we describe an LED-based multifurcated light guide and spectral light source that can provide illumination for spectral imaging at frame rates necessary for video-rate endoscopy. We also present an updated light source optical ray-tracing model that resulted in further optimization and provided a ∼10X light transmission increase compared to the initial prototype. Future work will iterate simulation and benchtop testing of the hyperspectral endoscopic system to achieve the goal of video-rate spectral endoscopy.

Dynamic Leukocyte Populations Are Associated With Early- and Late-stage Lesions in Hidradenitis Suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition typically targeting the axillary and anogenital regions of the body. The massive inflammatory cell infiltrate produced in this cryptogenic condition has led investigators in the attempt to link particular inflammatory cell fractions and cytokines to disease development, and ultimately to disease treatment. This study qualitatively and quantitatively analyzes the white blood cell fractions of macrophages, B-lymphocytes, T-lymphocytes, plasma cells, and granulocytes in 104 HS lesions on formalin-fixed paraffin-embedded tissues using immunohistochemistry (IHC). Four dermis-associated epithelial categories were investigated from persons with HS: 15 unaffected HS skin (US), 19 distended but unruptured follicle epithelium (UF), 62 migrating stratified squamous epithelium (MSSE) from ruptured follicles, and 35 degraded migrating epithelial sheets (DMES). In addition, 27 control skin (CS) from persons without HS were evaluated. Analysis of cell counts indicated that non-migratory dermal epithelium (CS, US, and UF) stimulated very little inflammatory response. However, contrary to previous studies which indicated macrophages to be the chief inflammatory cell in HS, this study showed that plasma cells were the primary cell type present in early-stage HS lesions (MSSE), whereas granulocytes were the major cell population seen in late-stage HS lesions (DMES).

RIPK1 Expression Associates With Inflammation in Early Atherosclerosis in Humans and Can Be Therapeutically Silenced to Reduce NF-κB Activation and Atherogenesis in Mice.

Chronic activation of the innate immune system drives inflammation and contributes directly to atherosclerosis. We previously showed that macrophages in the atherogenic plaque undergo RIPK3 (receptor-interacting serine/threonine-protein kinase 3)-MLKL (mixed lineage kinase domain-like protein)-dependent programmed necroptosis in response to sterile ligands such as oxidized low-density lipoprotein and damage-associated molecular patterns and that necroptosis is active in advanced atherosclerotic plaques. Upstream of the RIPK3-MLKL necroptotic machinery lies RIPK1 (receptor-interacting serine/threonine-protein kinase 1), which acts as a master switch that controls whether the cell undergoes NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells)-dependent inflammation, caspase-dependent apoptosis, or necroptosis in response to extracellular stimuli. We therefore set out to investigate the role of RIPK1 in the development of atherosclerosis, which is driven largely by NF-κB-dependent inflammation at early stages. We hypothesize that, unlike RIPK3 and MLKL, RIPK1 primarily drives NF-κB-dependent inflammation in early atherogenic lesions, and knocking down RIPK1 will reduce inflammatory cell activation and protect against the progression of atherosclerosis. We examined expression of RIPK1 protein and mRNA in both human and mouse atherosclerotic lesions, and used loss-of-function approaches in vitro in macrophages and endothelial cells to measure inflammatory responses. We administered weekly injections of RIPK1 antisense oligonucleotides to Apoe-/- mice fed a cholesterol-rich (Western) diet for 8 weeks. We find that RIPK1 expression is abundant in early-stage atherosclerotic lesions in both humans and mice. Treatment with RIPK1 antisense oligonucleotides led to a reduction in aortic sinus and en face lesion areas (47.2% or 58.8% decrease relative to control, P<0.01) and plasma inflammatory cytokines (IL-1α [interleukin 1α], IL-17A [interleukin 17A], P<0.05) in comparison with controls. RIPK1 knockdown in macrophages decreased inflammatory genes (NF-κB, TNFα [tumor necrosis factor α], IL-1α) and in vivo lipopolysaccharide- and atherogenic diet-induced NF-κB activation. In endothelial cells, knockdown of RIPK1 prevented NF-κB translocation to the nucleus in response to TNFα, where accordingly there was a reduction in gene expression of IL1B, E-selectin, and monocyte attachment. We identify RIPK1 as a central driver of inflammation in atherosclerosis by its ability to activate the NF-κB pathway and promote inflammatory cytokine release. Given the high levels of RIPK1 expression in human atherosclerotic lesions, our study suggests RIPK1 as a future therapeutic target to reduce residual inflammation in patients at high risk of coronary artery disease.

Circulatory condition in kidney patients with purulent pyelonephritis

Relevance. Urinary tract infections are among the most common infectiousdiseases encountered in the practice of doctors of various specialties, both at the outpatient and hospital stages. In recent years, there has been an increase in the incidence of acute pyelonephritis. The management of patients with acute complicated pyelonephritis requires further study aimed at optimizing the diagnostic algorithm and treatment methods. Objective. Studying the state of blood circulation in the kidney in patients with purulent pyelonephritis and improving the quality of treatment of these patients by introducing our own developed methodology. Materials and methods. In the Regional clinical hospital (Barnaul city, Russia), in the conditions of the urological department, the author personally examined and operated on 30 patients with purulent pyelonephritis according to his own method with an established diagnosis of purulent pyelonephritis. On the first day, all patients underwent retroperitoneoscopic decapsulation of the kidney on the affected side in combination with regional arterial infusion of alprostadil for 3 days. All patients underwent general clinical examination, multispiral computed tomography (MSCT) of the kidneys with bolus contrast enhancement, duplex scanning of renal vessels, and morphological examination of the material before and after the operation. Results. In all cases, the postoperative period proceeded favorably with a shorter treatment time. On the first day after surgery, patients noted a decrease in the intensity of pain in the area of the affected kidney. When comping the data of MSCT of the kidneys with bolus contrast, obtained in patients before treatment, the disappearance of foci of destruction in the kidney and a pronounced restoration of the previously lost blood flow of the kidney on the side of the lesion in the early stages are determined. Nephrectomy was not performed in any case. Conclusion. Each of the stages of the proposed method for the treatment of acute purulent pyelonephritis is an integral part of the technique as a whole; each stage is necessary to influence its level of the vascular bed and parenchyma in the area of its microabscesses and zones of infection. The method allows to achieve restoration of blood circulation in the kidney with the opening of antibiotics access to the organ parenchyma.

Our Experience with Nasolabial Flaps in Soft Tissue Reconstruction of Oral Malignancy; Feasible Option in Rural Set Up.

In this era of microvascular expertise, free flaps are the preferred option by reconstructive surgeons but has technical limitation in rural set up. Nasolabial flaps has been widely mentioned in literature for smaller defect reconstruction with minimal morbidity. It is a robust flap for soft tissue reconstruction in early stage lesion of oral cavity. We present a series of single stage oral cavity reconstruction using inferiorly based islanded nasolabial flaps in small to moderate soft tissue defects. This is a retrospective study which included biopsy proven 10 patients diagnosed with early stage oral cavity malignancy. All the patients underwent single stage islanded nasolabial flap for small to moderate oral defects. Follow up of all patients were recorded with respect to clinical photographs, mouth opening, tongue mobility, deglutition, speech and patient satisfaction. All operated patients had good functional outcome in terms of swallowing, speech and tongue mobility. All patients were satisfactory with the postoperative results. In early stage oral malignancy patients, this option justifies a reliable and cost effective approach. Inferiorly based islanded nasolabial flaps provides a single stage, safer, faster and reliable option for small to moderate oral cavity defects.

Fluoride rechargeable layered double hydroxide powders for dental applications

It has been widely reported that the prevention of early-stage carious lesions requires a sustained therapeutic low-level release of fluoride in the oral cavity. However dental caries remains as one of the most prevalent diseases worldwide. Therefore, there is a requirement for the development of a material capable of releasing fluoride at a therapeutic level. Layered double hydroxides (LDH) have the potential to achieve this by taking up and releasing fluoride repeatedly, such as recharging using a fluoride toothpaste/mouthwash. A range of fluoride rechargeable LDH powders; ZnAl, MgAl (1:1, 2:1 and 3:1) and CaAl (1:1 and 2:1) were successfully synthesised at different ratios and characterised (pXRD, FTIR, SEM and F− ISEs). NiAl LDH did not form an LDH structure at all ratios. The fluoride uptake (from sodium fluoride, NaF) and release (de-ionised water, DW) over two cycles (24 h) from these powders, demonstrated an increase in the LDH lattice interlamellar space and an increase in fluoride uptake in the following order of formulations; CaAl>MgAl>ZnAl LDH. 2:1 MgAl demonstrated the greatest fluoride release with the same amount released during release and re-release. Therefore, LDH has the potential to be incorporated into various applications, while altering the composition or ratio to obtain a desired fluoride uptake or release.

Efferocytic Defects in Early Atherosclerosis Are Driven by GATA2 Overexpression in Macrophages.

The loss of efferocytosis—the phagocytic clearance of apoptotic cells—is an initiating event in atherosclerotic plaque formation. While the loss of macrophage efferocytosis is a prerequisite for advanced plaque formation, the transcriptional and cellular events in the pre-lesion site that drive these defects are poorly defined. Transcriptomic analysis of macrophages recovered from early-stage human atherosclerotic lesions identified a 50-fold increase in the expression of GATA2, a transcription factor whose expression is normally restricted to the hematopoietic compartment. GATA2 overexpression in vitro recapitulated many of the functional defects reported in patient macrophages, including deficits at multiple stages in the efferocytic process. These findings included defects in the uptake of apoptotic cells, efferosome maturation, and in phagolysosome function. These efferocytic defects were a product of GATA2-driven alterations in the expression of key regulatory proteins, including Src-family kinases, Rab7 and components of both the vacuolar ATPase and NADPH oxidase complexes. In summary, these data identify a mechanism by which efferocytic capacity is lost in the early stages of plaque formation, thus setting the stage for the accumulation of uncleared apoptotic cells that comprise the bulk of atherosclerotic plaques.

Low-level laser therapy for the treatment of early stage cutaneous leishmaniasis: A pilot study.

Low-Level Laser Therapy (LLLT) has been investigated for the treatment of various dermatological disorders. Here, we investigate the efficacy of LLLT for the treatment of cutaneous leishmaniasis (CL). This study comprised of 53 patients (total 123 lesions) with a confirmed diagnosis of CL via positive smear of LD-bodies. The CL lesions were classified in Grade I (ie, papule of size ≤1 cm) to Grade V (ie, vesicle formation, ulceration, and superadded infection of size >4 cm). All the patients were divided into group 1 with low grade (ie, Grade I and II) CL lesions and group 2 with high-grade disease (ie, Grade III-V). Red laser light (wavelength = 635 nm) was used for the lesion irradiation, with a light dose of 75 J/cm2 and at a low power of 300 mW. The treatment was divided into four sessions, one session per week. Disease assessment at 10 months follow-up revealed complete response in 91% and partial response in 9% patients of group 1, while no response was observed in patients of group 2. LLLT offers a promising treatment modality for patients presenting with early-stage (ie, Grade I and II) CL lesions.

Comprehensive Dosimetric Evaluation of a Biology-Guided Radiotherapy Machine in Treatment Plans for Brain, Lung, Head and Neck, Esophagus, and Prostate Malignancies

A new biology-guided radiotherapy (BgRT) delivery machine is currently under development. It combines a compact 6 MV linear accelerator and a binary multileaf collimator with PET, kVCT, and MV imaging systems on the same ring gantry that rotates continuously at 60 rotations per minute while the patient is translated through the bore with small increments. We aimed to perform inter-comparison of treatment plans for typical clinical disease sites between the new BgRT machine and existing IMRT delivery techniques. To ensure objective comparison, biology guidance was not assumed in planning for the new system and the same planning margins were used for each case with all the delivery techniques. We retrospectively retrieved one clinical external-beam radiotherapy treatment plan for each of the five disease sites: intracranial lesion for stereotactic radiosurgery (SRS), early-stage lung lesion for stereotactic body radiotherapy (SBRT), head and neck, esophagus, and prostate with seminal vesicle and pelvic lymph node treatments. Both a helical tomotherapy (HT) plan (using a 1-cm or 2-cm jaw size) and a volumetric modulated arc therapy (VMAT) plan (using 0.5-cm MLC or 0.25-cm MLC leaves) were generated for each clinical case. A treatment plan (the prototype plan) for the new system was generated for each case using either a 1-cm jaw size for the intracranial SRS and lung SBRT plans, and a 2-cm jaw size for the other sites. Dosimetric constraints in national radiotherapy treatment protocols (RTOG-0813, NRG-HN001, RTOG-1010, and RTOG-0534) were used to facilitate dosimetric comparison of treatments plans. The prototype plans met all the dosimetric constraints in all disease sites. The relative strengths with each delivery technique differ with respect to the disease site. With the head & neck case, while the VMAT and HT plans shows similar normal organ dose, the prototype plan achieved comparable PTV dose coverage and lower dose to most critical organs including a 40% reduction in parotid mean dose compared to the HT and the VMAT plans. With the intracranial SRS case, the VMAT plan achieved slightly better dose conformity and faster dose drop-off compared to the HT and prototype plans, while all the plans achieved comparable dose to the normal brain and other organs-at-risk. With the lung SBRT case, both the VMAT and the prototype plans achieve similar dose to the normal lung volume and other organs. In both the prostate and esophagus cases, mixed results were observed with one technique achieving better sparing to certain organs. While all the delivery technique met given dosimetric constraints in most disease sites, the prototype system was shown to achieve better normal organ sparing with the head & neck site, while the VMAT technique with smaller MLC leaves was more suitable for intracranial SRS. Actual dosimetric measurements will follow to verify dose delivery accuracy with the new BgRT machine.

SQUAMOUS CELL CARCINOMA IN A PATIENT WITHOUT RISK FACTORS: A CASE REPORT

Spin cell carcinoma (SCC) is the most common oral malignant neoplasm, and the main risk factor is smoking. The objective of the study is to report an SCC case without risk factors. A 62-year-old female patient, nonsmoker, not elitist, was forwarded to the service for evaluation of lesion that had not healed for 6 months. On intraoral examination, a white, ulcerated lesion with hardened raised edges was observed, located on the side border of the tongue. The incisional biopsy was performed, and the histologic slices revealed epithelial tissue with ulcerated areas and presence of malignant epithelial cells in the shape of islands and cords invading the connective tissue. The diagnosis was compatible with SCC. The patient was referred to an oncologist, with whom the surgical treatment was performed. Detailed physical examination is essential regardless of whether they have risk factors for SCC or not to detect lesions in early stages.

Gastropathy associated with lanthanum phosphate deposition that was endoscopically tracked for 3\u2009years. A case report

BackgroundWith the recent increased use of lanthanum carbonate, several cases of lanthanum phosphate deposition to gastric mucosa in dialysis patients have been reported. However, the endoscopic appearance of the early-stage lesion and the over-time alterations of endoscopic findings due to the progression of lanthanum phosphate deposition remain unclear.Case presentationAn 80-year-old man receiving dialysis and taking lanthanum carbonate as a phosphate binder over a 4-year period underwent upper gastrointestinal endoscopy four times beginning 1 year after initiation of treatment. The first endoscopic examination (after 1 year of exposure to lanthanum carbonate) revealed rough mucosa with a few areas of white granular mucosa. Over the 3 years of endoscopic follow-up, the white granular mucosa spread and multiple erosions appeared. Histopathological findings of biopsy specimens from an erosion showed extensive infiltration by histiocytes containing deposits. Scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) revealed that the presence of the deposits containing phosphorus and lanthanum in the gastric mucosa.On the basis of these results, the patient was diagnosed with gastropathy associated with lanthanum phosphate deposition.ConclusionsOver a 3-year period, endoscopic findings associated with lanthanum deposition gradually changed and expanded from the early stage.

Detection of Oral Dysplastic and Early Cancerous Lesions by Polarization-Sensitive Optical Coherence Tomography.

Detection of oral dysplastic and early-stage cancerous lesions is difficult with the current tools. Half of oral cancers are diagnosed in a late stage. Detection of early stromal change to predict malignant transformation is a new direction in the diagnosis of early-stage oral cancer. The application of new optical tools to image stroma in vivo is under investigation, and polarization-sensitive optical coherence tomography (PS-OCT) is potentially one of those tools. This is a preliminary study to sequentially image oral stromal changes from normal, hyperplasia, and dysplasia to early-stage cancer by PS-OCT in vivo. We used 4-Nitroquinoline-1-oxide drinking water to induce dysplasia and early-stage oral cancer in 19 K14-EGFP-miR-211-GFP transgenic mice. A total of 8 normal, 12 hyperplastic, 11 dysplastic, and 4 early-stage cancerous lesions were enrolled. A new analytic process of PS-OCT imaging was proposed, called an en-face birefringence map. From the birefringence map, the sensitivity, specificity, positive predictive value, and negative predictive values to detect dysplasia and early-stage cancer were 100.00%, 95.00%, 93.75%, and 100.00%, respectively, and the kappa value of these images between two investigators was 0.942. The mean size of malignant lesions detected in this study is 1.66 ± 0.93 mm. This pilot animal study validates the use of PS-OCT to detect small and early-stage oral malignancy with high accuracy and consistency.

Abstract 2822: Single-cell evaluation to identify tumor-stroma niches driving the transition from in situ to invasive breast cancer

Abstract Introduction: Ductal carcinoma in situ is a non-invasive lesion of the breast that comprises ~20% of newly diagnosed breast cancers in the United States. Prospectively distinguishing indolent from aggressive lesions has been a major clinical challenge. To begin addressing these challenges, we use an experimentally tractable mouse model of breast cancer in which invasive (but rarely in situ) lesions display architectural and morphological abnormalities while also being heavily immune-infiltrated. Methods: To explore the tumor-stroma niches that evolve as breast cancer progresses, we are undertaking single cell RNA sequencing and imaging mass cytometry to identify tumor and immune cells present within in situ (early) versus invasive (advanced) lesions, and to characterize shifts in phenotype and tumor-stroma niches that may occur as breast cancer transitions from in situ to invasive disease. Results: Single cell analyses revealed major cell populations within the tumor compartment of both early and advanced disease, including luminal- and basal-like populations, as well as an additional minor population that appears to represent a unique intermediate between luminal and basal states. Early stage lesions were comprised primarily of the major luminal population, whereas advanced lesions exhibited a significant expansion of intermediate and basal populations, suggesting that breast cancer cells may undergo a transition from luminal-like to basal-like phenotype during progression to invasive disease. Analysis of the immune compartments of early versus advanced disease also revealed that the relative neutrophil/MDSC/S100A8+ population increased as lesions advanced, while B cells, NK cells, and some T cells decreased. Furthermore, the immune populations of advanced lesions exhibited widespread upregulation of IL-17 targets, suggesting that the IL-17 pathway may drive shifts in the immune microenvironmental to support disease progression, particularly the increase in neutrophils/MDSCs. Additionally, given a previously reported role of IL-17 to alter epithelial stemness, increased IL-17 signaling in advanced lesions may also be driving the potential luminal-to-basal transition of malignant cells. Conclusion: Taken together, these findings suggest that a subset of malignant epithelial cells may transition from luminal-like to basal-like cells, and that this transition may be driven and/or maintained by a commensurate increase in IL-17 signaling that both directly impacts tumor cells and also establishes a tumor-supportive microenvironment. Citation Format: Vidya C. Sinha, Mingchu Xu, Amanda L. Rinkenbaugh, Xinhui Zhou, Xiaomei Zhang, Helen Piwnica-Worms. Single-cell evaluation to identify tumor-stroma niches driving the transition from in situ to invasive breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2822.

Abstract CT113: A novel laser emission microscopy for early detection of colon cancer: Analysis of at-risk human colon from an interventional trial (research in progress)

Abstract Introduction: Accurate identification of neoplastic or pre-neoplastic lesions is traditionally dependent on microscopic identification of nuclear abnormalities. It is both time-consuming and challenging in early-stage lesions and difficult to detect. Laser-emission microscopy (LEM) that uses laser emission (not fluorescence) is an emerging technology that takes advantage of the finding that highly-proliferating cells like those in pre-neoplastic lesions can be distinguished from less proliferative cells by a lower laser emission dot density (LDD) when stained with a nuclear dye. We have successfully used this technique to detect (early) nuclear changes in a high-fat induced colon cancer model. LEM has also been used successfully to differentiate healthy tissue from cancerous tissue in human patients. Methods: This LEM system is capable of rapidly scanning tissue as large as 2 cm×2 cm in ~10 min. Both laser emission and regular fluorescence are imaged simultaneously, thus providing information regarding the lasing spot density and location within the human colon tissues. In this study, we employed colon biopsies from 12 human subjects (at risk for colorectal cancer). These subjects participated in a 90-day intervention, placebo-controlled, randomized trial. 8 subjects ingested known chemopreventives and 4 subjects took a placebo. Colon biopsies were taken from the sigmoid colon at baseline and after 90 days. The formalin-fixed, paraffin-embedded tissues were subjected to LEM microscopic assessment. For this, the tissues were sandwiched between two mirrors to form a laser cavity and laser excitation was applied. By comparing the laser emission spectra, highly proliferative tissue could be differentiated from less proliferative tissue. Post-treatment biopsies were compared to their baseline status. These biopsies were also stained with Ki67 to obtain their proliferation index to compare with the LEM results. Results: On average, there was a 20% increase in the LDD among the 8 subjects on chemopreventives while no change was seen in Ki67 positivity. In placebo group, Ki67 was decreased by 14% and LDD was 12% increased. On individual comparison, LDD and Ki67 data were correlated positively in 6 subjects. Conclusion: The preliminary data suggest that in histologically-normal but “at-risk” human colon LEM may pick early nuclear changes that may not be detected by a proliferation marker. Table.A comparison of lasing dot density (LDD) data to Ki67 positivity (Whole slide analysis*)Mean LDDPercent Positive NucleiChange RatioSubject IDPrePostPrePostLDDKi67Data correlated?Placebo 1491336504.75.40.741.15NoPlacebo 2851078159.28.70.920.95YesPlacebo 3573183558.96.01.460.67NoPlacebo 4659288469.76.71.340.69NoChemopreventive#1 1296733436.513.61.132.10YesChemopreventive#1 2528261406.57.71.161.20YesChemopreventive#1 3468453429.67.01.140.73NoChemopreventive#1 4758173358.25.60.970.68YesChemopreventive#2 1323046255.34.91.430.91NoChemopreventive#2 2508078408.29.11.541.11YesChemopreventive#2 35587400110.46.80.720.66YesChemopreventive#2 4491373226.94.91.490.71NoPlacebo combined1.12±0.340.86±0.23Chemopreventive combined1.20±0.281.01±0.49*Both mucosa and submucosa were involved in the analysis Citation Format: Muhammad N. Aslam, Yun-Lu Sun, Ingrid Bergin, Mohamed Ali H. Jawad-Makki, Karsten Knuver, Danielle (Kim) Turgeon, James Varani, Xudong Fan. A novel laser emission microscopy for early detection of colon cancer: Analysis of at-risk human colon from an interventional trial (research in progress) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT113.

The rates of second lung cancers and the survival of surgically-resected second primary lung cancers in patients undergoing resection of an initial primary lung cancer

BackgroundThe Lung Cancer Screening Trial demonstrated improved overall survival (OS) and lung cancer specific survival (LCSS), likely due to finding early-stage NSCLC. The purpose of our investigation is to evaluate whether long-term surveillance strategies (4+ years after surgical resection of the initial lung cancer(1LC)) would be beneficial in NSCLC patients by assessing the rates of second lung cancers(2LC) and the OS/LCSS in patients undergoing definitive surgery in 1LC as compared to 2LC (>48 months after 1LC) populations. MethodsSEER13/18 database was reviewed for patients during 1998–2013. Log-rank tests were used to determine the OS/LCSS differences between the 1LC and 2LC in the entire surgical group(EG) and in those having an early-stage resectable tumors (ESR, tumors <4 cm, node negative). Joinpoint analysis was used to determine rates of second cancers 4−10 year after 1LC using SEER-9 during years 1985–2014. ResultsThe rate of 2LCs was significantly less than all other second cancers until 2001 when the incidence of 2LCs increased sharply and became significantly greater than all other second cancers in females starting in year 2005 and in men starting in year 2010. OS/LCSS, adjusted for propensity score by using inverse probability weighting, demonstrated similar OS, but worse LCSS for 2LCs in the EG, but similar OS/LCSSs in the ESR group. ConclusionBecause the rate of 2LCs are increasing and because the OS/LCSS of the 1LC and 2LC are similar in early-stage lesions, we feel that continued surveillance of patients in order to find early-stage disease may be beneficial.

Skeletal Muscle Metastases from Carcinomas: A Review of the Literature.

* Bones are a common site for metastases; however, muscle metastases recently have been more commonly reported, not only as a result of the multidisciplinary approach in the treatment of these patients but also because of more sensitive imaging modalities such as positron emission tomography-computed tomography (PET-CT) that identify these lesions in early stages.* The most common carcinoma is lung carcinoma, with a hematogenous route of spread mainly to the axial region of the body (the psoas muscle, the gluteal muscles, and the paravertebral muscles). * Clinically, skeletal muscle metastases from carcinomas frequently present as painful palpable masses with or without swelling and are commonly found before diagnosis of the primary carcinoma.* Multiple imaging modalities, including radiographs, CT, magnetic resonance imaging (MRI), and PET-CT, have been used for diagnosis and staging, but tissue sampling is needed for a final diagnosis. The most important differential diagnosis of skeletal muscle metastases is with soft-tissue sarcomas.* Treatment is mainly based on chemotherapy and/or radiation; surgery is performed in cases of symptomatic lesions that fail to respond to nonoperative treatment.